RFC3 Inhibitors

Chemical classes termed RFC3 inhibitors would include agents that can either directly inhibit the RFC3 subunit of the Replication Factor C complex or indirectly impede its function through the modulation of associated pathways. Since direct inhibitors specifically targeting RFC3 are not documented or characterized, the focus is on indirect inhibition through the manipulation of cellular processes that RFC3 is involved in, such as DNA replication and repair.

RFC3 inhibitors interfere with DNA synthesis and repair. By disrupting these processes, they impose replication stress on cells, which in turn can affect the normal function of RFC3, as it is a critical component in the assembly of the replication machinery. DNA damage-inducing inhibitors add to replication stress by creating lesions on DNA that require the replication machinery to engage in repair processes, during which RFC3 plays a significant role. Furthermore, inhibitors impair the repair of DNA single-strand breaks by inhibiting PARP, can lead to the collapse of replication forks, a scenario where the RFC complex is essential for recovery and repair. Nucleoside analogs like gemcitabine and fludarabine are incorporated into DNA during replication, leading to chain termination and subsequent challenges to replication processes involving RFC3. UCN-01's inhibition of cell cycle-regulating kinases can alter the timing and progression of replication, indirectly affecting RFC3's function in coordinating DNA synthesis. Brefeldin A, though primarily affecting membrane transport, can also lead to a cellular environment that indirectly impacts DNA replication and the function of replication factors like RFC3.